Scientists create chemical compound that can reverse effects of potentially deadly drugs: Their method successfully counteracted two highly addictive drugs–fentanyl and methamphetamine–in lab experiments

Drug overdoses in the United States have risen sharply in the last two decades. Nearly 92,000 people died from overdoses of illegal drugs and prescription opioids in 2020 — more than five times the number of deaths in the year 2000 — and synthetic opioids like fentanyl are one of the main culprits.

Naloxone (an injectable medicine also marketed as the nasal spray Narcan) has saved countless lives, but it only works for opioid overdoses and has other limitations. Now, in an effort to identify a more universal treatment for drug overdose, a team of University of Maryland scientists tested a chemical compound — Pillar[6]MaxQ (P6AS) — as an antidote for methamphetamine and fentanyl. Their findings, published today in the journal Chem, were highly promising.

“Opioids already have a reversal agent in naloxone, but there are a variety of non-opioid drugs of abuse — like methamphetamine, PCP, mephedrone, ecstasy (MDMA) and cocaine — that do not have a specific antidote,” said the study’s lead author Lyle Isaacs, a professor in the Department of Chemistry and Biochemistry at UMD. “That’s one of the huge opportunities for our compound.”

In vitro and in vivo laboratory tests showed that P6AS successfully sequestered fentanyl and methamphetamine, a non-opioid stimulant, and mitigated their potentially deadly biological effects. Additional in vitro tests revealed that P6AS also binds strongly to other drugs, including PCP, ecstasy and mephedrone, which suggests that P6AS could someday be used to counteract a wide array of drugs.

The study was conducted by Isaacs’ lab in collaboration with researchers in UMD’s Department of Cell Biology and Molecular Genetics and Department of Psychology. Although the synthesis and chemical properties of P6AS were first documented in 2020 by Isaacs and Weijian Xue, a former post-doctoral associate in the Department of Chemistry and Biochemistry, this study reports its first in vivo applications.

P6AS works as a molecular container, which means that it binds and sequesters other compounds in its central cavity.

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